Mona S. Calvo

The Effects of High Phosphorus Intake on Calcium Homeostasis

Survey data confirm that the dietary pattern of many American women who are at high risk of developing osteoporosis is typically high in phosphorus and low in calcium. The imbalance between calcium and phosphorus intake may become more pronounced with continued changes in food preferences and the growing use of phosphorus-containing food additives. Recent studies in young women have shown that a high phosphorus diet moderately low in calcium results in a mild secondary hyperparathyroidism that persists over 4 weeks. Plasma levels of calcitriol did not change despite changes in PTH and serum ionized calcium. Studies on men have shown that dietary phosphorus at levels within the normal range of intakes can affect the renal production and serum concentration of calcitriol. High phosphorus intakes for ten days reduced their plasma calcitriol levels; a 70% reduction in phosphate intake significantly increased their plasma calcitriol. Thus, several lines of evidence indicate that prolonged high phosphorus intake may impair the usual homeostatic mechanisms that come into play when dietary calcium is limited. This, in turn, could impair achievement of maximal bone mass or accelerate bone loss. Although no clinical studies have linked high phosphorus intake with lower bone mass or higher rates of bone loss in humans, this relationship has been demonstrated in animal models. For example, young beagles fed high phosphorus, moderately low calcium diets showed a significant reduction in vertebral bone mass. Current dietary patterns of high phosphorus, low calcium consumption result in persistent changes in calcium regulating hormones that are not conducive to maximizing peak bone mass during growth or slowing the rate of aging bone loss. The net effect of the present dietary pattern on bone status, particularly in teenage and young adult women, needs to be determined. Optimal nutrition early in life, which may include higher calcium and lower phosphorus intakes, together with adequate exercise, may be the most cost-effective approach to the prevention of osteoporotic fractures.

Bioavailability of vitamin D2 from enriched mushrooms in prediabetic adults: a randomized controlled trial.

Background/Objectives:Based on the growing evidence of risk reduction from fresh fruit and vegetable consumption and an inverse relationship between serum 25-hydroxyvitamin D (25OHD) and the risk of type 2 diabetes (T2D), we determined the benefits of regularly consuming vitamin D-enriched mushrooms in a prediabetic cohort. Exposing edible mushrooms to ultraviolet B (UVB) light increases vitamin D2 (D2) and raises serum 25OHD2 in healthy young adults; however, their benefit to deficient prediabetics and glucose metabolism remains untested.Subjects/methods:Forty-three prediabetic, D-deficient adults (25OHD≤20 ng/ml), BMI>25 were randomized to four groups consuming daily entrées containing 100 g fresh sliced cooked mushrooms prepared by a chef for 16 weeks. Two groups were fed UVB-treated mushrooms initially containing: 600 IU D2 or 4000 IU D2; each one also received one capsule of placebo daily. Two control groups were fed untreated mushrooms and D3 dietary supplements at two label doses: 600 IU D3 and 4000 IU D3. D2 and D3 content were analyzed in mushrooms, before and after cooking and in over-the-counter supplements.Results:After 16 weeks, both D2-UVB-mushroom entrée doses, which were significantly lower after cooking, produced modest or no increases in 25OHD2 or total 25OHD relative to the positive control subjects who actually consumed about 1242 and 7320 IU per day of D3 (higher than stated on the label).Conclusions:Unanticipated D2 cooking loss from fresh UVB mushrooms and probable low absorption and/or hydroxylation may explain the smaller increase in 25OHD2 in our prediabetic overweight/obese cohort compared with past findings in younger, healthy subjects. Moreover, no dose or vitamin D source was associated with modifying T2D risk factors.

Nutrition and Lifestyle Effects on Vitamin D Status

Publisher Summary Vitamin D deficiency is a public health problem worldwide, even in countries with enough sunshine year round to promote adequate skin synthesis. The circulating level of the transport metabolite 25-hydroxyvitamin D (25(OH)D) is the most commonly used measure of vitamin D nutritional status. This chapter describes the determinants of vitamin D status, sun exposure, and dietary intakes, and the many factors that can affect these two sources of vitamin D. It emphasizes on lifestyle choices and environmental factors that either positively or negatively affect these determinants, thus affecting vitamin D status. Following this, it discusses the strategies to improve vitamin D status through safe sun exposure and appropriate dietary intakes. Vitamin D has many functions beyond its role in calcium and bone health, and with this new knowledge has come the recognition that vitamin D insufficiency and deficiency is at epidemic proportions worldwide. As an urgent public health concern, vitamin D deficiency has the potential to increase morbidity and mortality. Thus worldwide, each country faces the task of determining a level of vitamin D, whether from sun exposure, dietary intake including food fortification and supplements, or combinations of these, which will be effective at maintaining the appropriate level of vitamin D activity in the body.

Rationale and Plan for Vitamin D Food Fortification: A Review and Guidance Paper

Vitamin D deficiency can lead to musculoskeletal diseases such as rickets and osteomalacia, but vitamin D supplementation may also prevent extraskeletal diseases such as respiratory tract infections, asthma exacerbations, pregnancy complications and premature deaths. Vitamin D has a unique metabolism as it is mainly obtained through synthesis in the skin under the influence of sunlight (i.e., ultraviolet-B radiation) whereas intake by nutrition traditionally plays a relatively minor role. Dietary guidelines for vitamin D are based on a consensus that serum 25-hydroxyvitamin D (25[OH]D) concentrations are used to assess vitamin D status, with the recommended target concentrations ranging from ≥25 to ≥50 nmol/L (≥10–≥20 ng/mL), corresponding to a daily vitamin D intake of 10 to 20 μg (400–800 international units). Most populations fail to meet these recommended dietary vitamin D requirements. In Europe, 25(OH)D concentrations <30 nmol/L (12 ng/mL) and <50 nmol/L (20 ng/mL) are present in 13.0 and 40.4% of the general population, respectively. This substantial gap between officially recommended dietary reference intakes for vitamin D and the high prevalence of vitamin D deficiency in the general population requires action from health authorities. Promotion of a healthier lifestyle with more outdoor activities and optimal nutrition are definitely warranted but will not erase vitamin D deficiency and must, in the case of sunlight exposure, be well balanced with regard to potential adverse effects such as skin cancer. Intake of vitamin D supplements is limited by relatively poor adherence (in particular in individuals with low-socioeconomic status) and potential for overdosing. Systematic vitamin D food fortification is, however, an effective approach to improve vitamin D status in the general population, and this has already been introduced by countries such as the US, Canada, India, and Finland. Recent advances in our knowledge on the safety of vitamin D treatment, the dose-response relationship of vitamin D intake and 25(OH)D levels, as well as data on the effectiveness of vitamin D fortification in countries such as Finland provide a solid basis to introduce and modify vitamin D food fortification in order to improve public health with this likewise cost-effective approach.

Vitamin D research and public health nutrition: a current perspective

This 2017 special issue of Public Health Nutrition features nineteen research manuscripts all relevant to the role of vitamin D nutritional status in the risk and prevention of chronic diseases of public health importance. A useful barometer gauging the worldwide growing interest in vitamin D and health research is shown by over 13 000 studies abstracted in PubMed over the last 5 years alone, all with a focus on vitamin D. Vitamin D deficiency in Europe is associated with adverse health outcomes whose direct and indirect medical cost burdens have been estimated in the hundreds of billions of Euros, which underlines the importance of this work to public health. Dedicating a special issue to these recently accepted vitamin D studies provides Public Health Nutrition editors with an opportunity to set in perspective the diverse aspects of the continued growing interest in vitamin D nutritional status, its health importance, and the impact of the many recent innovations in analytical methods, assay standardization programmes and the underlying factors contributing to the controversy over serum cut-off values defining vitamin D nutritional status. Newer standardized analytical methods now enable research exploring the many gaps in our understanding of vitamin D nutritional status which many of these papers address, as well as the association with reduced risk of disease and other beneficial health effects. The common feature among all the papers in this special vitamin D issue is the measurement of vitamin D status or the circulating concentrations of 25-hydroxyvitamin D (25 (OH)D, nmol/l or ng/ml). There is a growing demand to assess vitamin D status in order to screen for deficiency, monitor efficacy of supplementation or fortification, or assess the association between vitamin D status and chronic diseases including osteoporosis, diabetes, cancer, CVD, infection and autoimmune or neurological disorders. To meet this demand, less labour-intense assay methods have been developed along with certified external standards and proposed criteria for defining vitamin D deficiency/sufficiency. The goal of this perspective is to inform researchers about the currently accepted assay methods and quality control procedures used to determine 25(OH)D concentrations and the most widely accepted criteria for establishing vitamin D status. We present some background information describing relevant new evidence in four areas defining important public health gaps in knowledge that are addressed by many of the studies in this issue. Our intent is to provide insight into how these studies contribute to these gaps in our understanding of vitamin D status and, more importantly, how the study findings may impact public health nutrition policy and practices.

Vitamin D Fortification in North America: Current Status and Future Considerations

Until the last decade, adequacy of vitamin D status was not a public health concern, because vitamin D synthesis from sun exposure was thought to meet most of the North American populations’ needs and the ubiquitous fortification of milk was thought to provide sufficient intake when sun exposure was limited. More recently, a growing incidence of rickets in infants and evidence from national surveys showing high prevalence of poor vitamin D status in children and adults is slowly eroding our confidence in the vitamin D adequacy of many Americans and Canadians, as well as in other developed countries [1–3]. Concern about the high prevalence of poor vitamin D status stems from the significant association of low plasma 25-hydroxyvitamin D {25(OH)D} levels with the increased risk of both chronic and infectious disease, but most strongly with the chronic bone diseases, osteoporosis, and rickets in children [1–4].

Global prevalence and disease burden of vitamin D deficiency: a roadmap for action in low- and middle-income countries: Vitamin D deficiency: a roadmap for action

Vitamin D is an essential nutrient for bone health and may influence the risks of respiratory illness, adverse pregnancy outcomes, and chronic diseases of adulthood. Because many countries have a relatively low supply of foods rich in vitamin D and inadequate exposure to natural ultraviolet B (UVB) radiation from sunlight, an important proportion of the global population is at risk of vitamin D deficiency. There is general agreement that the minimum serum/plasma 25‐hydroxyvitamin D concentration (25(OH)D) that protects against vitamin D deficiency–related bone disease is approximately 30 nmol/L; therefore, this threshold is suitable to define vitamin D deficiency in population surveys. However, efforts to assess the vitamin D status of populations in low‐ and middle‐income countries have been hampered by limited availability of population‐representative 25(OH)D data, particularly among population subgroups most vulnerable to the skeletal and potential extraskeletal consequences of low vitamin D status, namely exclusively breastfed infants, children, adolescents, pregnant and lactating women, and the elderly. In the absence of 25(OH)D data, identification of communities that would benefit from public health interventions to improve vitamin D status may require proxy indicators of the population risk of vitamin D deficiency, such as the prevalence of rickets or metrics of usual UVB exposure. If a high prevalence of vitamin D deficiency is identified (>20% prevalence of 25(OH)D < 30 nmol/L) or the risk for vitamin D deficiency is determined to be high based on proxy indicators (e.g., prevalence of rickets >1%), food fortification and/or targeted vitamin D supplementation policies can be implemented to reduce the burden of vitamin D deficiency–related conditions in vulnerable populations.

Molecular Mechanisms of Adverse Health Effects Associated With Excess Phosphorus Intake

Excess phosphorus intake has always been a concern in patients with chronic kidney disease because of their impaired ability to excrete phosphorus loads and the known association between excess phosphorus and health complications, including cardiovascular disease, in this population. More recently, large epidemiological studies suggest that mild elevations of serum phosphate still within the normal range are associated with cardiovascular disease risk in healthy populations without evidence of kidney disease. In healthy adults with functional kidneys, phosphorus balance is achieved when serum concentrations are maintained in a very narrow range, which requires a sustained balance between urinary loss and net phosphorus absorption from the gastrointestinal tract. This balance is carried out through a complex organ network, the bone–kidney–intestine network, which operates through complex, ordered endocrine negative feedback loops involving parathyroid hormone, fibroblast growth factor-23, Klotho, and vitamin D and several tissue-specific cellular phosphate transporters. Disruption of this ordered endocrine regulation has been shown to result in the type of tissue damage associated with some chronic disease risks. Excess phosphorus consumption, well beyond the level of required nutrient intake, is a key suspect in the possible disruption of the endocrine regulation of phosphorus balance and may be associated with chronic disease risk in adults with normal renal function. The increased cumulative use of phosphorus ingredients in food processing in modern society together with our increasing knowledge about new endocrine pathways that may connect phosphorus intake and pathology raises the issue of the potential toxicity of an essential mineral such as phosphorus when taken in excess. This chapter summarizes what is currently known about phosphate homeostasis, the mechanisms involved in its regulation, and related pathologies in patients with chronic kidney disease as well as in the general population.